ESPE Abstracts (2022) 95 P1-112

ESPE2022 Poster Category 1 Growth and Syndromes (85 abstracts)

Long-term follow-up of aromatase-inhibitor use in 3 family members with aromatase excess syndrome

Eleni Giannopoulou 1 , Stephanie Brandt 1 , Martin Schmidt 2 , Maki Fukami 3 & Martin Wabitsch 1


1University Medical Centre, Department of Paediatrics and Adolescent Medicine, Division of Paediatric Endocrinology and Diabetes, Ulm, Germany; 2Institute of Biochemistry II, Hospital of the Friedrich-Schiller-University, Jena, Germany; 3Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan

Introduction: Aromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced extraglandular aromatization of androgens and estrogen excess. Genomic rearrangements in chromosome 15q21 are found to result in overexpression of the aromatase gene CYP19A1. In males it is characterized by pre- or peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only a few female patients have been described so far. The aim of this study is to report on a family with 4 family members with EAXS and to present the long-term effects of aromatase-inhibitor use in 3 of them.

Patients and Methods: 3 children (index patient, brother, sister) with AEXS treated with 3rd generation aromatase inhibitor, letrozole, were studied. Genetic analysis of the aromatase gene showed a 0.3-Mb deletion in 15q21, involving six of the CYP19A1 exons 1, all exons of GLDN, and DMXL2 exons 2-43, in the index patient, his father and his siblings.

Results: The index patient (male, 8 years old) presented with gynecomastia, accelerated growth and bone age (13 6/12 years). With start of puberty, estradiol levels increased, whereas testosterone and androstenedione levels remained low. Gynecomastia progressed and a mastectomy was performed twice (ages 9 and 13 years). Presuming AEXS, a therapy with letrozole was initiated first at the age of 19 years. Although adult height was already reached (168 cm), low-dose letrozole treatment increased testicular volume, promoted virilization, improved physical strength and libido. No gynecomastia was observed under treatment. His younger brother presented at the age of 3 years with accelerated bone age (5 6/12 years). Treatment with letrozole was started at the age of 7 years. Under treatment the patient developed no gynecomastia and reached a final height of 179 cm. His sister, who presented at the age of 6 years with premature thelarche, accelerated growth and bone age (10 6/12 years), was treated with an estrogen receptor modulator (tamoxifen) followed by letrozole treatment for 1 year. Menarche occurred at age 13 6/12 years and final height was 158 cm.

Discussion/Conclusion: We observed a phenotypic variability within family members with AEXS carrying the same genetic microdeletion in CYP19A1. When started early, treatment with aromatase inhibitors in children with AEXS was found to prevent the development of gynecomastia and improve final height. In adult life, treatment with aromatase inhibitors in a very low dose resulted in improved physical strength and libido.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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